Multimorbidity disease clusters are associated with venous thromboembolism: an extended cross-sectional national study.

Multimorbidity, i.e., two or more non-communicable diseases (NCDs), is an escalating challenge for society. Venous thromboembolism (VTE) is a common cardiovascular disease and it is unknown which multimorbidity clusters associates with VTE. Our aim was to examine the association between different common disease clusters of multimorbidity and VTE. The study is an extended (1997-2015) cross-sectional Swedish study using the National Patient Register and the Multigeneration Register. A total of 2,694,442 Swedish-born individuals were included in the study. Multimorbidity was defined by 45 NCDs. A principal component analysis (PCA) identified multimorbidity disease clusters. Odds ratios (OR) for VTE were calculated for the different multimorbidity disease clusters. There were 16% (n = 440,742) of multimorbid individuals in the study population. Forty-four of the individual 45 NCDs were associated with VTE. The PCA analysis identified nine multimorbidity disease clusters, F1-F9. Seven of these multimorbidity clusters were associated with VTE. The adjusted OR for VTE in the multimorbid patients was for the first three clusters: F1 (cardiometabolic diseases) 3.44 (95%CI 3.24-3.65), F2 (mental disorders) 2.25 (95%CI 2.14-2.37) and F3 (digestive system diseases) 4.35 (95%CI 3.63-5.22). There was an association between multimorbidity severity and OR for VTE. For instance, the occurrence of at least five diseases was in F1 and F2 associated with ORs for VTE: 8.17 (95%CI 6.32-10.55) and 6.31 (95%CI 4.34-9.17), respectively. In this nationwide study we have shown a strong association between VTE and different multimorbidity disease clusters that might be useful for VTE prediction.

A hypothesis - generating Swedish extended national cross-sectional family study of multimorbidity severity and venous thromboembolism.

OBJECTIVES: Venous thromboembolism (VTE) is a common worldwide disease. The burden of multimorbidity, that is, two or more chronic diseases, has increased. Whether multimorbidity is associated with VTE risk remains to be studied. Our aim was to determine any association between multimorbidity and VTE and any possible shared familial susceptibility. DESIGN: A nationwide extended cross-sectional hypothesis - generating family study between 1997 and 2015. SETTING: The Swedish Multigeneration Register, the National Patient Register, the Total Population Register and the Swedish cause of death register were linked. PARTICIPANTS: 2 694 442 unique individuals were analysed for VTE and multimorbidity. MAIN OUTCOMES AND MEASURES: Multimorbidity was determined by a counting method using 45 non-communicable diseases. Multimorbidity was defined by the occurrence of ≥2 diseases. A multimorbidity score was constructed defined by 0, 1, 2, 3, 4 or 5 or more diseases. RESULTS: Sixteen percent (n=440 742) of the study population was multimorbid. Of the multimorbid patients, 58% were females. There was an association between multimorbidity and VTE. The adjusted odds ratio (OR) for VTE in individuals with multimorbidity (2 ≥ diagnoses) was 3.16 (95% CI: 3.06 to 3.27) compared with individuals without multimorbidity. There was an association between number of diseases and VTE. The adjusted OR was 1.94 (95% CI: 1.86 to 2.02) for one disease, 2.93 (95% CI: 2.80 to 3.08) for two diseases, 4.07 (95% CI: 3.85 to 4.31) for three diseases, 5.46 (95% CI: 5.10 to 5.85) for four diseases and 9.08 (95% CI: 8.56 to 9.64) for 5 ≥ diseases. The association between multimorbidity and VTE was stronger in males OR 3.45 (3.29 to 3.62) than in females OR 2.91 (2.77 to 3.04). There were significant but mostly weak familial associations between multimorbidity in relatives and VTE. CONCLUSIONS: Increasing multimorbidity exhibits a strong and increasing association with VTE. Familial associations suggest a weak shared familial susceptibility. The association between multimorbidity and VTE suggests that future cohort studies where multimorbidity is used to predict VTE might be worthwhile.

Increased ß-cell volume in mice fed a high-fat diet: a dynamic study over 12 months.

As we previously demonstrated, there is an adaptive increase in insulin secretion in insulin resistance in the model of high-fat fed female mice. Since it is assumed that islets also adapt to insulin resistance with ß-cell expansion, we have now examined beta volume in this experimental model. Female C57BL/6JBomTac mice were therefore fed a high-fat diet (60% fat from lard) for three, six or twelve months and beta cell volume was estimated as ß-cell area per islet, individual ß-cell size, and ß-cell number per islet. Control animals were fed a normal chow (11% fat). We found that ß-cell area per islet and total number of beta cells per islet were increased already after three months of high-fat feeding and that this increase was sustained throughout the twelve month study period. In contrast, individual beta cell size showed a dynamic pattern with a reduction after three months followed by increase after six and twelve months. The number of apoptosis (caspase-3) positive ß-cells was reduced after three months, whereas there was no difference in proliferation (Ki-67) positive cells, although these were generally rarely observed. Thus, we conclude that insulin resistance accompanying high-fat feeding in mice is followed by progressive ß-cell expansion as evident by early increased islet ß-cell volume and total number of ß-cells, whereas individual ß-cell size showed a dynamic response. The model is also associated with an early reduced apoptosis, which may contribute to the increased beta cell volume.